Bortezomib-Cyclophosphamide-Dexamethasone versus Rituximab in PGNMID

Area of Science:

• Nephrology
• Immunology
• Hematology

Background:

• Proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) is a rare kidney disease with limited evidence for prospective treatments.
• Current treatments often involve clone-directed therapies, but comparative data are lacking.

Purpose of the Study:

• To evaluate the feasibility and preliminary efficacy of plasma cell-targeted therapy (bortezomib-cyclophosphamide-dexamethasone, BCD) versus B-cell-targeted therapy (rituximab, RTX) in patients with PGNMID.
• To compare renal response rates, proteinuria, serum albumin, and estimated glomerular filtration rate (eGFR) between the two treatment groups.

Main Methods:

• A single-center, open-label, pilot randomized controlled trial (RCT) involving 20 eligible patients with PGNMID.
• Patients were randomized (1:1) to receive either 6 cycles of BCD or 4 weekly doses of RTX (375 mg/m²), with a potential RTX booster dose.
• Primary endpoint was overall renal response at 12 months; secondary outcomes included proteinuria, albumin, eGFR, and safety.

Main Results:

• Overall renal response at 12 months was 60% for BCD and 70% for RTX (P=1.0).
• Both treatments reduced proteinuria and improved serum albumin over 12 months.
• BCD showed a transient eGFR decline at 6 months, recovering by 12 months; safety profiles were manageable.

Conclusions:

• Both BCD and RTX demonstrated renal responses in this exploratory PGNMID trial.
• Findings are hypothesis-generating due to small sample size and open-label design.
• Larger, multicenter studies are required to establish optimal PGNMID therapy.